Background: Rural Tennessee, especially rural East Tennessee has seen a dramatic increase in rates of controlled drug prescriptions and controlled drug overdose deaths in recent years. However, little is known about the individual decisions to prescribe or continue prescriptions with relation to addiction concerns. Objectives: The purpose of this study was to learn more about what factors lead to physicians’ prescribing control drugs for non-cancer pain through the use of focus groups. Methods: A qualitative study, using focus groups, in five family medicine clinics in East Tennessee and Southwest Virginia. The investigators used a semi-structured interview guide designed to facilitate group discussions about prescription drug abuse and misuse. Results: There were four main themes identified by the focus groups: (1) prescribers’ changing prescribing patterns over time; (2) factors that influence controlled drug prescribing; (3) use and barriers to using state prescription drug monitoring programs (PDMPs); (4) prescribing controlled drugs to women of childbearing age. Each theme had several subthemes. Conclusions: The balance between treating the patient's symptoms and causing potential harm is a challenge. The patient's pain cannot be ignored, but the potential harm of opioid therapy is not taken lightly. As the public health concern of prescription drug abuse in rural Appalachia continues to spread, prescribers are aware of their connection to the problem, and ultimately the solution.

Bakgrund  Opioidepidemin som pågår ses som ett globalt folkhälsoproblem där ökad förskrivning av receptbelagda opioider spelar en central roll. Opioider kan orsaka lidande och i många fall en för tidig död. Patienter har ofta negativa upplevelser av sjukvården. Vårdpersonal saknar vanligen utbildning och upplever rädsla för att vårda denna patientgrupp. Syfte Syftet var att beskriva patienters upplevelser av opioidanvändning och opioidberoende. Metod En icke-systematisk litteraturöversikt utfördes. Med hjälp av relevanta sökord som bland annat “opioid related disorder”, “substance use disorder” och “patient perspective” för föreliggande syfte togs de inkluderade artiklarna fram från databaserna CINAHL och PubMed. För att säkerställa att artiklarna var av god kvalitet granskades de utifrån Sophiahemmets högskolas bedömningsinstrument. Därefter utfördes en integrerad analys som resulterade i fyra olika teman. Resultat Litteraturöversiktens resultat beskriver patienternas upplevelser av opioidanvändning och opioidberoende. Resultatet ger kunskap om patienternas upplevelser av att påbörja och avsluta användning av opioider, sambandet mellan smärta och opioidanvändning samt upplevelsen av stigmatisering. Även en kunskapsbrist kring opioiders beroendeframkallande effekt beskrivs i studien. Slutsats Resultatet av litteraturöversikten kan öka kunskap och förståelse kring betydelsen av vägledande och fullständig information som bör ges till patienter gällande opioider. Genom att informera om, samt öka patienternas förståelse om opioider kan detta förhoppningsvis minska risken att utveckla beroende. För att kunna garantera en hållbar utveckling ur ett holistiskt perspektiv är vårdpersonal i behov av lämpliga verktyg och förutsättningar för att kunna bidra till en säker behandling och god omvårdnad. / Background The ongoing opioid epidemic is seen as a global public health problem, where increased prescribing of prescription opioids has a significant role. Opioids can cause suffering and, in many cases, premature death. Patients often have negative experiences of healthcare. Nursing staff do not usually have enough education and experience fear of caring for this patient group. Aim The aim of this study was to describe patients' experiences of opioid use and opioid dependence. Method A non-systematic literature review was performed. Using relevant keywords such as “opioid related disorder”, “substance use disorder” and “patient perspective” for the present purpose, the included articles were retrieved from the CINAHL and PubMed databases. To ensure that the articles were of good quality, they were examined on the basis of Sophiahemmet University's assessment instrument. An integrated analysis was then performed, resulting in four different themes. Results The results of the literature review were based on 16 scientific articles of both qualitative and quantitative design. The results provide knowledge about patients' experiences of living with opioids, the connection between pain and opioid use and the experience of stigma. A lack of knowledge about the addictive effect of opioids is also described in the study. Conclusions The results of the literature review can increase knowledge and consideration about the importance of guiding and complete information that should be given to patients regarding opioids. By informing them about and increasing patients' understanding of opioids, this can hopefully reduce the risk of developing addiction. In order to guarantee sustainable development from a holistic perspective, care staff need suitable tools and conditions to be able to contribute to safe treatment and good nursing.

This study was designed to explore the hormonal regulation of CNS opioid peptide levels in female Sprague Dawley rats. Forty-eight animals were divided into 2 equal groups for acute and chronic studies. Each group was further divided into 4 subgroups, each containing 6 animals. Each rat in the control group received an inert pill (in 0.25 ml corn oil daily by gavage); the second group, 15 μg norethindrone (NE, a potent progestin present in the oral contraceptive Micronor®); the third group, 15 μg NE and 1 μg ethinyl estradiol, EE2 (present in the oral contraceptive Modicon®) and the fourth group, 10 times the dose of the third group. Rats were treated either acutely for 5 days or chronically for 7 weeks. Opioid peptides were estimated by radioimmunoassay. Acute administration of 150 μg NE + 10 μg EE2 decreased the levels of methionine-enkephalin (ME), leucine-enkephalin (LE), dynorphin (DYN) and β-endorphin like immunoreactivity (β-EI) by about 50% in the pituitary. The same dose on chronic administration also decreased DYN, but increased the levels of ME and LE in the pituitary by 331 and 69%, respectively. In the hypothalamus, chronic administration of NE + EE2 increased the level of ME (155%) and LE (87%) as well as of DYN (97%). In the striatum, the levels of LE (33%) and DYN (115%) were elevated during chronic administration. It is concluded that the acute administration of NE + EE2, in general, reduces the levels of ME, LE, DYN and β-EI. The extent of this decrease is about the same in the pituitary, hypothalamus and striatum. Chronic administration of these hormones, however, results in a reversal of this decrease (except for β-EI) and actually can increase the levels of ME, LE and DYN in all three tissues.

Release of endomorphin (ENDO)-2 like substances from the dorsal horn of the isolated rat spinal cord was measured by the immobilized-antibody microprobe technique. Spinal cords were removed from anesthetized 4-6 week old rats and superfused with oxygenated Krebs solution at room temperature. Glass microprobes coated with ENDO-2 antibodies were inserted into the dorsal horn of the lumbar spinal cord 1.5 mm lateral to the midline to a depth 2.5 mm below the dorsal surface of the cord. Each probe remained in situ for 10 min periods before, during and after electrical stimulation applied to the dorsal root entry zone of the same spinal segment. There was no detectable basal release of immunoreactive endomorphin-2 like substance (irENDO) from the dorsal horns during the pre-stimulation, nor following the stimulation period. A significant release of irENDO was measured during the electrical stimulation. These results provide the first evidence of a irEndo release that is correlated spatially with the dorsal horn laminae I and II where ENDO-2-immunoreactive fibers are concentrated in the dorsal horn in response to electrical activation of primary afferent fibers.

Neuropathic pain in a common problem encountered in palliative care. When neuropathic pain is diagnosed, appropriate treatment is important in limiting the severe psychosocial impairment that can ensue with undertreated pain. Proper evaluation of the patient to clarify the type of pain experienced is the first step to determine appropriate management. Tapentadol is an oral mu-opioid receptor agonist and a noradrenaline reuptake inhibitor developed by Ortho-McNeil Janssen Pharmaceuticals and approved by the Food and Drug Administration in November 2008 for the treatment of moderate-to-severe acute pain in adult patients and for chronic pain in August 2011 in an extended release form. Tapentadol has been studied for use in nociceptive pain but few studies have yet been done to assess its efficacy in the treatment of neuropathic pain.

1. Whole-cell patch recordings were made from antidromically identified sympathetic preganglionic neurons (SPN) of immature rat spinal cord slices. Bath application of nociceptin (0.1-1 μmol/L) suppressed excitatory postsynaptic potentials (EPSP) and hyperpolarized a population of SPN; these effects were naloxone (1 μmol/L) insensitive. 2. Nociceptin suppressed the amplitude of EPSP without causing a concomitant change in glutamate-induced depolarizations, suggesting a presynaptic inhibitory action. 3. Analysis of current-voltage relationships showed that nociceptin hyperpolarized SPN by increasing an inwardly rectifying K+ current. 4. Intrathecal injection of nociceptin (3, 10 and 30 nmol) to urethane-anaesthetized rats dose-dependently reduced the mean arterial pressure and heart rate; these effects were not prevented by prior intravenous injection of naloxone (1 mg/kg). 5. Results from our in vitro and in vivo experiments suggest that nociceptin suppresses spinal sympathetic outflow either by attenuating excitatory synaptic responses or hyperpolarizing SPN.

Opioid use disorder (OUD) is one of the most pressing public health problems of our time, with staggering morbidity, social impact, and economic costs. Prescription opioids play a critical role in the opioid crisis as they increase exposure and availability in the general population, making them an attractive target for much needed prevention and risk mitigation strategies. Opioid exposure, including legitimate prescription use, leads to a variety of physiologic adaptations (e.g. dependence) that may be leveraged to understand and identify risk of misuse. Mobile health (mHealth) tools, including wearable sensors have great potential in this space, but have been underutilized. Of specific interest are digital biomarkers, or end-user generated physiologic or behavioral measurements that correlate with events of interest, health, or pathology. Preliminary data support the concept that wearable sensors can detect digital biomarkers of opioid use and may provide clues regarding individual physiologic adaptations to opioid use over time. This dissertation follows a path though the exploration and refinement of these digital biomarkers of opioid use in various clinical use cases. Longitudinal data from individuals treated with opioids for acute pain will be explored through various machine learning models to detect opioid use and to explore patient and treatment factors that impact model performance. Next, a signal processing approach will be undertaken to explore the effects of opioid agonism in a different population of individuals- those presenting with opioid toxicity and precipitated withdrawal. Both approaches will be combined to further refine the digital biomarker capabilities, this time with a focus on the difference between opioid naive and chronic users. And finally, usability, facilitators and barriers to use of a sensor-based monitoring system for opioids will be evaluated through a qualitative lens. Taken together, theses data support the development of a smart technology, driven by empirically derived algorithms which can be used to monitor opioid use, support safe prescribing practices, and reduce OUD and death.

Bakgrund: Substanssyndrom är en kronisk sjukdom som kommer till följd av långvarigt bruk av narkotika. Det finns cirka 29 500 personer i Sverige som har ett utvecklat substanssyndrom. Riskfaktorer kan vara tidigare trauma, uppväxt och ärftlighet. Substanssyndromet påverkar hälsan både psykiskt och fysiskt och leder till ett lidande. Stigmatisering av fenomenet finns i samhället. Det behövs ytterliggare kunskap för att sjuksköterskan ska kunna tillgodose patientens behov. Syfte: Beskriva vuxna personers upplevelser av att leva med substanssyndrom. Metod: En kvalitativ analys har gjorts på bloggar skrivna av personer som själva lider av substanssyndrom. Etiska överväganden har gjorts för att anonymisera personerna bakom bloggarna. Resultat: I resultatet framkommer personers upplevelser under tre huvudkategorier; känna tillhörighet i en ny miljö, när drogerna tar över och att inte orka leva under drogernas påverkan. Konklusion: Mer förståelse för hur personer upplever sin beroendeproblematik krävs för att sjuksköterskan ska kunna möta patienten och ha kunskap för att ge rätt vård. / Background: Substance syndrome is a chronic disease that results from long-term drug use. There are about 29,500 people in Sweden who have a developed substance syndrome. Risk factors can be past trauma, upbringing and heredity. The substance syndrome affects health both mentally and physically and leads to suffering. Stigmatization of the phenomenon exists in society. Additional knowledge is needed for the nurse to be able to meet the patient's needs. Aims: To describe adult’s experiences of living with substance abuse syndrome. Method: A qualitative analysis has been made on blogs written by people who themselves suffer from substance syndrome. Ethical considerations have been made to anonymize the people behind the blogs. Results: The result shows people's experiences under three main categories; feel a sense of belonging in a new environment, when the drugs take over and not being able to live under the influence of the drugs. Conclusion: More understanding of how people experience their addiction problems is required for the nurse to meet the patient and have the knowledge to provide the right care.

In man the metabolic heat produced during physical exercise stresses the thermoregulatory system, particularly if hot, humid environmental conditions prevail. It has recently been postulated that endogenous opioids may play a role in regulating body temperature at rest and because it has also been shown that blood levels of these substances increase during exercise, the possibility exists that endogenous opioids may play a role in thermoregulation during exercise. A study was conducted in two parts to determine the thermoregulatory response during exercise with and without pharmacologic blockade of the opioid receptor. In Part I nine healthy male subjects performed 30 minutes cycling at 50 % maximal aerobic capacity in an environmentally controlled laboratory. The subjects received either placebo, 2mg or 10mg naloxone hydrochloride in a randomized double-blind crossover fashion prior to the exercise test. Rectal temperatures were recorded at one-minute intervals and cardiorespiratory parameters were measured during the test. Water loss was calculated from differences in nude body weight. In part II eight male subjects performed a graded maximal cycle ergometer test after receiving either placebo or 2mg naloxone in a randomized double-blind crossover fashion. Rectal and sublingual temperatures were recorded before and after the test and oesophageal temperature was recorded at one-minute intervals during the test. Cardiorespiratory parameters were recorded during the test. The results of Part I show that rises in rectal temperature as well as calculated water losses were similar for placebo and after the administration of both 2mg and 10mg naloxone. Similarly, during maximal exercise (Part II) the rise in rectal and oesophageal temperatures was equivalent for placebo and 2mg naloxone but sublingual temperature failed to rise during exercise following the 2mg naloxone dose. Cardiorespiratory responses did not differ between placebo and naloxone tests in both Part I and Part II of the study. These results indicate that naloxone-mediated blockade of opioid receptors does not affect rectal and oesophageal temperature responses to either submaximal or maximal exercise. Naloxone appears to selectively alter the sublingual temperature response to exercise possibly by altering local blood flow. It is concluded that insofar as naloxone induced opioid receptor blockade provides a measure of the function of the endogenous opioid system, this study suggests that the endogenous opioid system does not play a significant role in thermoregulation during exercise.

The purpose of this scholarly project was to evaluate an evidence-based quality improvement program implemented in 2016 in a clinical practice setting to curtail overprescribing of opioids for noncancer pain management. In 2001, the National Pharmaceutical Council and The Joint Commission on Accreditation and Hospital Accreditation initiated a standard of practice for opioid use in noncancer pain management that resulted in opioid overprescribing and a 200% increase in opioid-related deaths and incalculable societal costs. Primary care providers including nurse practitioners issue the greatest number of opioid prescriptions; therefore, to address the problem of opioid overprescribing, the 2016 Centers for Disease Control and Prevention guidelines for opioid administration were implemented as a quality improvement program in a primary care setting with 10 providers. Lewin's change model was the vehicle for change and included an ongoing audit developed for tracking provider prescribing rates. The project sought to determine if adoption of the opioid administration guidelines reduced the prescribing rates in a clinical practice setting and thereby justify expanding the program to other primary clinic sites. A pre- post-single group comparison was conducted of prescribing rates from May 15, 2015 prior to implementing the guidelines and December 19, 2016 after the guidelines were in place. Analysis from t tests indicated a 41% (p < .01) reduction in prescribing rates. The project promotes positive social change through the decreased individual and societal cost of opioid- related deaths.